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Biomedical subjects

C Moore

Publications and source records attributed to C Moore.

At least 163 records · Page 9Linked to original sources

1H-magnetic resonance spectroscopy of the left temporal and frontal lobes in schizophrenia: clinical, neurodevelopmental, and cognitive correlates.

Twenty eight schizophrenic patients and 20 normal volunteers underwent proton magnetic resonance spectroscopy (MRS) on the left temporal and frontal lobe regions. Male patients showed a significant reduction in frontal but not temporal n-acetylaspartate (an intraneuronally distributed metabolite) in comparison with either male controls or female patients; frontal choline was raised in male patients relative to these groups. Putative neurodevelopmental indices, including obstetric complications, family history of schizophrenia, and minor physical anomalies, proved unrelated to MRS resonances. However, multiple aspects of memory function in patients were related to temporal but not frontal creatine, a pattern that was not apparent among controls. These MRS findings complement some previous structural MRI studies and much clinical and epidemiological evidence of important gender differences in schizophrenia. The findings also suggest that memory dysfunction in patients with schizophrenia may be associated with a particular pattern of temporal lobe metabolism on MRS.

Adult↗

Determination of sertraline and desmethylsertraline in human serum using copolymeric bonded-phase extraction, liquid chromatography and gas chromatography-mass spectrometry.

The determination of the new antidepressant drug sertraline and its main metabolite, desmethylsertraline, in human serum is described. A new solid-phase extraction method employing the dual functionality Clean Screen cartridge is presented followed by reversed-phase liquid chromatographic (LC) analysis. The sample preparation yielded extremely clean extracts and absolute recoveries in excess of 90% for both drugs from human serum. The response of the LC system was linear over the concentration range 0.01-2.5 mg/l for both sertraline and desmethylsertraline with a limit of detection of 0.01 mg/l. A gas chromatographic-mass spectrometric (GC-MS) system is also described should confirmation of the drugs be necessary.

1-Naphthylamine↗

Confirmation of benzodiazepines in urine as trimethylsilyl derivatives using gas chromatography-mass spectrometry.

A confirmation procedure for the identification and quantitation of various benzodiazepines in urine is presented. The urine sample is first hydrolyzed enzymatically because of the glucuronide conjugation of some benzodiazepine metabolites, then extracted using bonded-phase columns. After elution into an organic solvent, the samples are evaporated, converted to the trimethylsilyl ether derivatives and analyzed by electron ionization GC-MS. Quantitation was performed using selected-ion monitoring for each benzodiazepine using prazepam as the internal standard. The method provides excellent linearity and sensitivity for the trimethylsilyl derivatives.

Benzodiazepines↗

Tat-mediated delivery of heterologous proteins into cells.

The Tat protein of human immunodeficiency virus 1 (HIV-1) can enter cells efficiently when added exogenously in tissue culture. To assess if Tat can carry other molecules into cells, we chemically cross-linked Tat peptides (residues 1-72 or 37-72) to beta-galactosidase, horseradish peroxidase, RNase A, and domain III of Pseudomonas exotoxin A (PE) and monitored uptake colorimetrically or by cytotoxicity. The Tat chimeras were effective on all cell types tested, with staining showing uptake into all cells in each experiment. In mice, treatment with Tat-beta-galactosidase chimeras resulted in delivery to several tissues, with high levels in heart, liver, and spleen, low-to-moderate levels in lung and skeletal muscle, and little or no activity in kidney and brain. The primary target within these tissues was the cells surrounding the blood vessels, suggesting endothelial cells, Kupffer cells, and/or splenic macrophages. Tat-mediated uptake may allow the therapeutic delivery of macromolecules previously thought to be impermeable to living cells.

ADP Ribose Transferases↗

Immunology in the pediatrician's office.

The development of antibody-mediated immunity is reflected in the maturation of B lymphocytes, in the changing levels of total immunoglobulins, and in the development of specific antibodies first to proteins and then sequentially to different types of polysaccharides. The measurement of anti-pneumococcal antibodies allows us to recognize specific antibody deficiencies, which need to be differentiated from normal developmental phases in the maturation of antibody-mediated immunity. The recognition of the late phase of IgE mediated allergic reactions is important to understanding the chronic manifestations of allergy. Chronic manifestations of allergy are frequently missed because they do not appear to be clearly related to acute triggers of allergic reactions. These conditions can be appropriately diagnosed, prevented, and treated, however, when the mechanisms of the late manifestations of allergy are understood. The integration of knowledge about the development of immunity and of allergic diseases enhances the pediatrician's ability to care for patients with immunologic abnormalities.

Acute Disease↗

Physiological relevance of tumor necrosis factor in mediating macrophage-Leydig cell interactions.

Previously, we reported that testicular macrophages constitutively release tumor necrosis factor (TNF) in vitro and are unresponsive to bacterial endotoxins [lipopolysaccharides (LPS)]. These properties are not typical of other tissue macrophages. The goals of the present study were, therefore, to establish 1) if testicular macrophages also release TNF in vivo, and 2) if secretion of TNF in vitro is influenced by the isolation procedure. In vivo TNF production was assessed by assaying testicular interstitial fluid for TNF. Using the L929 cytotoxicity assay for TNF, we found that interstitial fluid contained a cytotoxic factor(s), but this bioactivity was not due to either authentic TNF or a TNF-like molecule acting through the TNF receptor. This was established by showing that 1) antibodies to TNF alpha and -beta could not neutralize interstitial fluid cytotoxicity; 2) interstitial fluid was cytotoxic to TNF-resistant L929 cells; and 3) there was no detectable TNF immunoreactivity in interstitial fluid, as measured by enzyme-linked immunosorbent assay. Therefore, we evaluated whether the release of TNF in vitro was induced by the isolation procedure, particularly by collagenase, which is used to free interstitial cells. Testicular macrophages obtained without the use of collagenase (agitation of testes in buffer) did not release TNF, but responded to the TNF-releasing effect of LPS. Exposure of peritoneal macrophages to collagenase resulted in constitutive TNF release in vitro and lack of responsiveness to LPS. There was no evidence that a non-TNF cytotoxic factor was released in the conditioned medium by any macrophage preparation. Taken together, our findings show that testicular macrophages do not constitutively release TNF, and collagenase has a significant activating effect on macrophages. Testicular macrophages will, however, release TNF when exposed to LPS, indicating that TNF could be a paracrine regulator of testicular steroidogenesis under pathological conditions.

Animals↗

White-tailed deer as a potential reservoir of Ehrlichia spp.

We determined the antibody prevalence to Ehrlichia spp., in white-tailed deer (Odocoileus virginianus) and the geographic distribution of seropositive animals in 84 counties in Alabama, Arkansas, Florida, Georgia, Illinois, Kentucky, Louisiana, Maryland, Massachusetts, Mississippi, Missouri, North Carolina, South Carolina, Tennessee, Texas, Virginia, and West Virginia (USA). Using an indirect fluorescent antibody test we detected antibodies (> or = 1:128) to this bacterium in 544 (43%) of 1269 deer. Presence of antibodies to Ehrlichia spp. was related to a southerly latitude, low elevation, and resulting milder climatic conditions. It appears that white-tailed deer were naturally infected with Ehrlichia spp.; the infection was widely distributed throughout the southeastern United States. Based on these data, we propose that white-tailed deer play a role in the natural history of Ehrlichia spp. infection in the United States.

Animals↗

Detection of cocaine, norcocaine, and cocaethylene in the meconium of premature neonates.

Our objective was to investigate the methodologic detection of cocaine abuse during pregnancy by determining the viability of meconium analysis for cocaine and its metabolites using chromatographic procedures as an alternative to urine testing using enzyme multiplied immunoassay technique. Our design was as follows: meconium and urine were taken from 106 very low birthweight premature babies. Meconium analysis for cocaine and its metabolites using extraction and chromatographic analysis was compared with the criterion standard immunoassay testing for urine. The work was carried out at The University of Chicago Hospital, Department of Pediatrics and the University of Illinois at Chicago, Department of Pharmacodynamics. Our patients were very low birthweight, premature babies (mean birthweight 1109 g; mean gestational age 29.1 weeks). Gender was evenly divided between male and female. The outcome measures were as follows: two active metabolites, norcocaine and cocaethylene, were detected in the meconium, but not in the urine, of some of the neonates. Determination of cocaine exposure in the newborn influenced assignment of babies in research studies as well as psychosocial evaluation and subsequent treatment of the neonate. Our results were: of the 106 meconium samples analyzed, 21 (19.8%) were positive for cocaine (n = 19, 0.24-0.78 mg/kg), norcocaine (n = 7, 0.10-0.56 mg/kg), cocaethylene (n = 1, 0.12 mg/kg) or combinations thereof. Benzoylecgonine was not detected in any of the samples. Of the urine samples analyzed by immunoassay, only 8 (7.5%) were positive for cocaine metabolites. We conclude that meconium is a better sample than urine for determining cocaine exposure in utero.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗

A human vascular disorder, supravalvular aortic stenosis, maps to chromosome 7.

The pathogenesis of vascular disease is unclear, but genetic factors play an important role. In this study we performed linkage analyses in two families with supravalvular aortic stenosis, an inherited vascular disorder that causes narrowing of major arteries and may lead to cardiac overload and failure. DNA markers on the long arm of chromosome 7 (D7S371, D7S395, D7S448, and ELN) were linked to supravalvular aortic stenosis in both families with a combined logarithm of likelihood for linkage (lod score) of 5.9 at the ELN locus. These findings indicate that a gene for supravalvular aortic stenosis is located in the same chromosomal subunit as elastin, which becomes a candidate for the disease gene.

Aortic Valve Stenosis↗

Pilot study of ambulatory infusional ifosfamide admixed with carboplatin.

BACKGROUND: Ifosfamide and carboplatin are agents that have completed Phase I studies using a continuous infusion schedule for as long as 14 days. The in vitro compatibility of the two drugs allows for the simultaneous administration in an admixture, and a pilot study was undertaken to determine the feasibility and tolerability of the infusion schedule for the combination. METHODS: Ifosfamide at 500 mg/M2/day and carboplatin at 15 or 20 mg/M2/day were administered for 14-day cycles repeated at 28 days in 29 patients, with a total of 60 courses administered. RESULTS: Total cumulative dose per cycle was: ifosfamide 7.0 g/M2 and carboplatin 210-280 mg/M2. Hematuria developed in five patients, four of whom had prior urologic disease, severe thrombocytopenia, or pelvic radiation. In all patients, the hematuria was transient and inconsequential despite the absence of mesna. Grade 3 or 4 leukopenia was observed in eight patients with or without thrombocytopenia and delayed subsequent treatment cycles. Thrombocytopenia was less frequent (Grade 3, 2 patients: Grade 4, 1 patient). No significant episodes of sepsis or hemorrhage were noted. Anemia requiring transfusion developed in 12 of 29 patients. Twenty-one of the 29 patients had received prior chemotherapy. Five of seven previously untreated patients with non-small cell lung cancer achieved a complete (1) or partial (4) response. CONCLUSIONS: A continuous 14-day infusion of ifosfamide admixed with carboplatin is feasible in an ambulatory setting with no need for adding mesna for urologic protection and full dosage administration for each agent. Phase 2 studies in non-small cell lung cancer would be reasonable at the optimal doses of ifosfamide 500 mg/M2/day and carboplatin 15 mg/M2/day, and the potential exists for the introduction of additional agents, such as etoposide.

Antineoplastic Combined Chemotherapy Protocols↗

A Darwinian function for the orbital cortex.

The relationship between evolutionary theory and human psychobiology suffers from a lack of bridging theory concerning Darwinian brain functions. This problem is addressed within the context of the theory that the human brain calculates Darwinian strategies for the long-term organization of behavior. This theory of brain function is tested using the literature of abnormal psychology, particularly phenotypes that appear to lack strategic evaluation of fitness outcomes. It is argued that sociopaths lack such "fitness-calculation", and therefore their behavior leads to reduced fitness, notwithstanding the absence of psychiatric pathology. Accidental, surgical, and congenital lesions to the orbital cortex of the frontal lobes can produce similar behavior, suggesting that the orbital cortex is the seat of strategic fitness-calculation. This bridge between Darwinian theory and brain function opens the way for formal theories of human behavior couched in terms of imminent Darwinian calculation.

Behavior↗

Otopalatodigital syndrome type II associated with omphalocele: report of three cases.

We present 3 patients with otopalatodigital (OPD) syndrome type II and omphalocele; 2 of the cases are brothers. There are now 6 known cases of OPD type I or II with omphalocele. We propose that this combination is not coincidental and discuss mechanisms that may result in the combination of OPD, omphalocele, and other midline defects.

Abnormalities, Multiple↗

Haloperidol and clozapine treatment and their effect on M-chlorophenylpiperazine-mediated responses in schizophrenia: implications for the mechanism of action of clozapine.

Since clozapine is, in contrast to conventional neuroleptics, effective in treatment refractory schizophrenic patients its mechanism of action may be different from that of typical neuroleptics. Clozapine has been shown to display the highest binding affinity of all neuroleptics to one of the serotonin (5-hydroxytryptamine, 5HT) receptor subtypes, i.e., the 5HT1c receptor. Furthermore, clozapine, in contrast to conventional neuroleptics, blocks the effect of 5HT agonists on ACTH and corticosterone release in animals. This study hypothesized that clozapine, but not haloperidol would block ACTH and prolactin release induced by the 5HT agonist, m-chlorophenylpiperazine (MCPP). MCPP (0.35 mg/kg PO) was administered after a 3-week drug-free period, after 5 weeks of haloperidol treatment (20 mg/day) and finally after 5 weeks of clozapine treatment (> 400 mg/day) in ten male schizophrenic patients. Clozapine, but not haloperidol, blocked the effect of MCPP on ACTH and prolactin release. These results suggest that clozapine, in contrast to haloperidol, is a functional 5HT antagonist. Since MCPP-induced ACTH and prolactin release may be (partially) 5HT1c mediated, these results suggest that clozapine is a potent antagonist at the 5HT1c receptor.

Adrenocorticotropic Hormone↗